The A3 adenosine receptor, a Gi protein-associated cell surface receptor, was proposed as a target to combat cancer and inflammation. The receptor is highly expressed in various tumor cell types while expression in adjacent normal tissues is relatively low. Activation of the receptor by a specific synthetic agonist induces modulation of downstream signal transduction pathways which include the Wnt and the NF-kB, resulting in tumor growth inhibition (1-5).
In vivo studies have shown that A3 adenosine receptor (A3AR) agonists inhibit the development of colon, prostate and pancreatic carcinomas as well as melanoma and hepatoma. A3AR agonists were also been shown to act as anti-inflammatory agents by ameliorating the inflammatory process in different experimental autoimmune models such as rheumatoid arthritis, Crohn's disease and multiple sclerosis (6-10).
The A3AR was found to be highly expressed in inflammatory tissues (synovia and paw) derived from adjuvant (AIA) and collagen induced arthritis experimental models (11). This over expression was reflected in the PBMNC of the animals. Treatment of ALA rats with an A3AR agonist resulted in disease amelioration and receptor down-regulation. In patients with Rheumatoid arthritis (RA), the receptor was found to be highly expressed in peripheral blood mononuclear cells (PBMNC) (11). Moreover, in a group of RA patients that was treated with an A3 AR agonist, a direct correlation was found between A3AR expression at baseline and response of the patients to the drug (12).
An increase was also found in the level of A3 adenosine receptor expression in the peripheral blood mononuclear cells (PBMNC) of subjects suffering from psoriasis as compared to the PBMNC of a healthy subject. This finding paved the way for the use of the A3AR expression level as a means for the diagnosis of a psoriasis state (13)
Psoriasis is a chronic condition. People often experience flares and remissions throughout their life.
There are several forms of psoriasis, and each form has unique characteristics that allow dermatologists to visually identify psoriasis to determine what type, or types, of psoriasis is present. Sometimes a skin biopsy will be performed to confirm the diagnosis. The main types of psoriasis include the following:
Plaque Psoriasis (reddened areas a few inches across covered by silvery scales)
Pustular Psoriasis (blisters of noninfectious pus on red skin)—Arthritic Psoriasis or Psoriatic Arthritis
Guttate Psoriasis (small, red spots on the skin)
Inverse or Flexural Psoriasis (shiny, red patches in areas of friction such as in the folds of skin in the groin, the armpits or under the breasts)
Erythroderma Psoriasis (reddening and scaling of most of the skin).
Treatment depends on the severity and type of psoriasis. Some psoriasis is so mild that the person is unaware of the condition. A few develop such severe psoriasis that lesions cover most of the body and hospitalization is required. These represent the extremes. Most cases of psoriasis fall somewhere in between. Psoriasis treatments fall into 3 categories:
Topical (applied to the skin);—Mild to moderate psoriasis;
Phototherapy (light, usually ultraviolet, applied to the skin)—Moderate to severe psoriasis;
Systemic (taken orally or by injection or infusion)—Moderate, severe or disabling psoriasis.
The treatment options can clear psoriasis for a period of time. Each treatment has advantages and disadvantages, and what works for one patient may not be effective for another.
In an article published on the internet (16), it is stated that (1-deoxy-1-[N6-(3-iodobenzyl)-adenin-9-yl]-N-methyl-β-D-ribofuronamide, IB-MECA, an A3AR agonist) could be applicable in indications such as inflammatory bowel disease and psoriasis.